Identification

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Name
AP5346
Accession Number
DB04992
Type
Small Molecule
Groups
Investigational
Description

AP5346 is designed to target a diaminocyclohexane platinum (Pt) moiety to tumors through pH-sensitive linkage to a 25 kDa hydroxypropylmethacrylamide polymer. It is being pursued by Access Pharmaceuticals, Inc.

Synonyms
Not Available
External IDs
AP5346
International/Other Brands
ProLindac
Categories
UNII
Not Available
CAS number
Not Available
Weight
Not Available
Chemical Formula
Not Available
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

Pharmacology

Indication

For the treatment of various forms of cancer.

Pharmacodynamics

Preclinical studies of the delivery of platinum to tumors in an animal model has shown that, compared with oxaliplatin at equitoxic doses, AP5346 delivers in excess of 16 times more platinum to the tumor. An analysis of tumor DNA, which is the main target for anti-cancer platinum agents, has shown that in excess of 13 times more platinum tumor DNA complexes were formed from AP5346 than oxaliplatin in these studies. Results from preclinical efficacy studies conducted in the B16 and other tumor models have also shown that AP5346 is superior to oxaliplatin in inhibiting the growth of tumors.

Mechanism of action

Utilizing the biocompatible water-soluble polymer HPMA as a drug carrier, AP5346 links DACH platinum to the polymer in a manner which permits the selective release of platinum in tumors. The polymer capitalizes on the biological differences in the permeability of blood vessels at tumor sites versus normal tissue. In this way, tumor selective delivery and platinum release is achieved. Once delivered to the tumor, platinum binds preferentially to the guanine and cytosine moieties of DNA, leading to cross-linking of DNA, thus inhibiting DNA synthesis and function.

TargetActionsOrganism
UDNANot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Rice JR, Gerberich JL, Nowotnik DP, Howell SB: Preclinical efficacy and pharmacokinetics of AP5346, a novel diaminocyclohexane-platinum tumor-targeting drug delivery system. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2248-54. [PubMed:16609041]
  2. Campone M, Rademaker-Lakhai JM, Bennouna J, Howell SB, Nowotnik DP, Beijnen JH, Schellens JH: Phase I and pharmacokinetic trial of AP5346, a DACH-platinum-polymer conjugate, administered weekly for three out of every 4 weeks to advanced solid tumor patients. Cancer Chemother Pharmacol. 2007 Sep;60(4):523-33. Epub 2007 Feb 17. [PubMed:17308894]
  3. Sood P, Thurmond KB 2nd, Jacob JE, Waller LK, Silva GO, Stewart DR, Nowotnik DP: Synthesis and characterization of AP5346, a novel polymer-linked diaminocyclohexyl platinum chemotherapeutic agent. Bioconjug Chem. 2006 Sep-Oct;17(5):1270-9. [PubMed:16984138]
  4. Van der Schoot SC, Nuijen B, Sood P, Thurmond KB 2nd, Stewart DR, Rice JR, Beijnen JH: Pharmaceutical development, quality control, stability and compatibility of a parenteral lyophilized formulation of the investigational polymer-conjugated platinum antineoplastic agent AP5346. Pharmazie. 2006 Oct;61(10):835-44. [PubMed:17069422]
External Links
PubChem Substance
347909880

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
Not Available
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

1. DNA
Kind
Nucleotide
Organism
Humans
Pharmacological action
Unknown
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da

Drug created on October 21, 2007 16:23 / Updated on June 04, 2019 06:14